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Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders

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Abstract

Vitamin D3 (VD) is a secosteroid hormone and shows a pleiotropic effect in brain-related disorders where it regulates redox imbalance, inflammation, apoptosis, energy production, and growth factor synthesis. Vitamin D3’s active metabolic form, 1,25-dihydroxy Vitamin D3 (1,25(OH)2D3 or calcitriol), is a known regulator of several genes involved in neuroplasticity, neuroprotection, neurotropism, and neuroinflammation. Multiple studies suggest that VD deficiency can be proposed as a risk factor for the development of several age-related neurological disorders. The evidence for low serum levels of 25-hydroxy Vitamin D3 (25(OH)D3 or calcidiol), the major circulating form of VD, is associated with an increased risk of Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), dementia, and cognitive impairment. Despite decades of evidence on low VD association with neurological disorders, the precise molecular mechanism behind its beneficial effect remains controversial. Here, we will be delving into the neurobiological importance of VD and discuss its benefits in different neuropsychiatric disorders. The focus will be on AD, PD, and HD as they share some common clinical, pathological, and epidemiological features. The central focus will be on the different attributes of VD in the aspect of its anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholinesterase activity, and psychotropic effect in different neurodegenerative diseases.

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Abbreviations

VD:

Vitamin D3

mVDR:

Membrane Vitamin D receptor

nVDR:

Nuclear Vitamin D receptor

VDRE:

Vitamin D response element

1-alpha:

V25-dihydroxyvitamin D3 (1a,25-(OH)2D3) or calcitriol

25:

hydroxyvitamin D3 or 25(OH)D3 or calcidio

GPCR:

G-protein-coupled receptors

MAPK:

Mitogen-activated protein kinases

ERK:

Extracellular signal-regulated kinase

AKT:

Protein kinase B

cAMP:

Cyclic adenosine monophosphate

PKA:

Protein kinase A

PLC:

Phospholipase C

PIP2:

Phosphatidylinositol 4,5-bisphosphate

DAG:

Diacylglycerol

IP3:

1,4,5-Trisphosphate

Ca+2 :

Calcium

RXR:

Retinoid X receptor

CREB:

CAMP response element-binding protein

IL-10:

Interleukin 10

IL-4:

Interleukin 4

TGF:

β-Transforming growth factor-β

BDNF:

Brain-derived neurotrophic factor

NGF:

Nerve growth factor

GDNF:

Glial cell line-derived neurotrophic factor

NT-3:

Neurotrophin-3

NT-4:

Neurotrophin-4

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Acknowledgements

We thank CSIR (Council of Scientific and Industrial Research) for MSKV’s SRF fellowship. MSKV, SAM, and OE are grateful for institutional fellowships provided by BITS-Pilani, Hyderabad. KG is obligated to DBT (BT/INF/22/SP42551/2021) for its research associate fellowship.

Funding

This work is supported by the SERB-SURE grant, Science and Engineering Research Board, Government of India (SUR/2022/000980), DBT builder grant, Department of Biotechnology (DBT; BT/INF/22/SP42551/2021), Government of India, the Young Maternity Parenthood grant award by the International Brain Research Organization (IBRO-2021).

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  1. Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India

    Manjari SKV, Sharon Mariam Abraham, Omalur Eshwari, Kishore Golla, Shuvadeep Maity & Pragya Komal

  2. Centre for Research in Neuroscience and Brain Program, The Research Instituteof the, McGill University Health Centre , Montreal, QC, Canada

    Priya Jhelum

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The manuscript and figures were prepared by MSKV, SAM, OE, KG, PJ, SM, and PK. The manuscript and figures were reviewed and edited by MSKV and PK. All authors read and approved the final manuscript.

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SKV, M., Abraham, S.M., Eshwari, O. et al. Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03989-w

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